Greetings from the Chairs
What an exciting and productive fall our committee has had! We’ll start by welcoming our newest committee members – the Biomarkers of Nephrotoxicity Working Group. Members of this Group bring several years of experience in miRNA biomarker discovery, which is well aligned with other projects ongoing in our group. We’re thrilled to have you in our committee!

Our annual face-to-face meeting was held in October at the HESI headquarters. In addition to a wonderful opportunity to catch up in person on the incredible advances our members have made in genomic applications within and outside our committee’s portfolio, this meeting always stimulates fantastic discussions on new potential projects and direction. This year we had lively conversations surrounding refining the name and mission of our committee. Stay tuned as we bring the top suggestions to you for your consideration in the very near future. We are also committed to finalizing our committee’s best practices, which will provide clear guidance on procedures. A new initiative this year is provision of an annual survey to ensure that members are knowledgeable and have access to key project information and resources available to our committee, and are fully engaged in the projects most relevant to their interests. Finally, in addition to hearing updates from our workgroup leads, we had enthusiastic debates and discussions about future projects, many of which are already well into development phases. We sincerely thank those members who brought forth proposals and we look forward to working with you in finalizing project plans that will maximize committee engagement.

We also congratulate several of our working groups on recent successes. Huge congratulations to the Biomarker Qualification Working Group, who had their validation exercise published in Proceedings of the National Academy of Sciences . In addition, this Working Group secured a letter of support from the FDA, an important first step towards formal qualification of the TGx-DDI transcriptomic biomarker, the first of its kind to undergo this process. The FFPE Working Group’s most recent manuscript was also accepted in Toxicological Sciences , which is an exciting development . The research detailed in the manuscript demonstrates how to significantly improve the RNA quality of formalin-preserved tissues to yield the highest quality of RNA-sequencing data, which will provide a powerful approach that enables transcriptomic analyses of FFPE archives.

We look forward to working with our membership in the coming months to develop initiatives arising from our annual meeting discussions. 

- Alison Harrill and Carole Yauk
Working Group Updates
Qualification of a Genomic Biomarker Approach to Provide Context to Positive Findings in in vitro Chromosome Damage Assays 
Chair: Dr. Jiri Aubrecht, Pfizer

In 2017, the project team submitted a qualification package to the US FDA to consider a first ever transcriptomic biomarker for regulatory qualification. Upon review, the US FDA’s Center for Drug Evaluation and Research (CDER) sent a formal Letter of Support encouraging the HESI Genomics Committee’s continued development of the TgX-DDI biomarker. This intensive effort by the committee to develop the biomarker approach and prepare the qualification package will enhance understanding and utilization of signature-based biomarkers for risk assessments. The biomarker panel is currently under active review by the U.S. Food and Drug Administration for possible formal qualification. The validation study is available as an open access publication online in Proceedings of the National Academy of Sciences (PNAS) titled “Development and validation of a high-throughput transcriptomic biomarker to address 21st century genetic toxicology needs” as of December 4, 2017. 
Biomarkers of Nephrotoxicity
Chairs: Drs. Jean-Charles Gautier, Sanofi & Ernie Harpur, Newcastle University

The Biomarkers of Nephrotoxicity Committee is delighted to merge with the HESI Genomics Committee this year. Currently, the Committee is completing confirmatory work to further assess the kidney region-specificity of miRNA biomarker candidates in rat nephron segments isolated by laser capture microdissection (LCM). LCM samples will be analyzed by digital droplet PCR (ddPCR), Firefly analysis, and Next Gen sequencing. Companies are optimizing and harmonizing ddPCR protocols and finalizing material transfer agreements. Additionally, Committee members are working to finish a manuscript regarding best practices for urinary protein biomarkers. 
Technical Considerations for RNA-Seq of FFPE Tissues
Chair: Dr. Susan Hester, US EPA

This workgroup has been researching the effects of formalin fixation on RNA-seq profiles, developing metrics for quality assessment of FFPE RNA, and investigating methods for improving the quality of RNA, and RNA-seq data from FFPE samples since 4Q 2015. Findings from this work were published in Toxicological Sciences in an article titled “Demodifying RNA for Transcriptomic Analyses of Archival Formalin-Fixed Paraffin-Embedded Samples” on December 7th. The group’s work will also be presented at the annual 2018 SOT meeting as a Roundtable Session, “Unlocking the ‘Omics Archive: Enabling Toxicogenomic/Proteomic Investigation from Archival Samples (ID 137)”. A second publication on RNA quality metrics is currently in development, and will be submitted for publication in 2018. Future studies will test the applicability of existing archival RNA-seq reverse-damage methods to DNA-seq of human tumor samples to assess variant profiles. This is an important translational step and will have implications for the field of precision medicine and biomarker discovery.
miRNA Biomarkers
Chairs: Drs. Brian Chorley, US EPA; Tatiana Sharapova, AbbVie

We welcome Dr. Tatiana Sharapova from AbbVie as our new co-chair for the workgroup. We also thank Dr. Alison Harrill and Dr. Aaron Smith for their previous service as chairs. As continuation of the rat miRNA atlas work in 2016, workgroup members are currently investigating cellular localization of candidate miRNAs in normal rodent liver using in situ hybridization to assess potential biomarkers of biliary injury. A new proposal is also being considered to measure these candidate miRNAs in serum as biomarkers of cellular-specific responses to chemical toxicity. In September 2017, Dr. Lansing Taylor and Dr. Lawrence Vernetti of the University of Pittsburg presented to the committee the development of their liver and vascular microphysiologic systems (MPS). These and future meetings will help define potential applications of measuring miRNAs in MPS as well as direct future committee efforts and collaborations.
Events Update
Genomics Committee Webinar Series - December 2017

In December we were pleased to host the inaugural talk for our new webinar series titled "Development of a Transcriptomics Reporting Framework (TRF) to guide the application of 'omics data in chemical hazard assessment". A huge thank-you to Dr. Timothy Gant of Public Health England for the highly informative webinar presentation describing efforts that have paved the way for a new OECD project to produce a ‘reference baseline analysis’ and ‘transcriptomics reporting framework’. The work he presented builds upon an early microarray/toxicity database and animal gene studies led by the HESI Genomics Committee more than a decade ago. We had over 50 attendees online to hear the presentation. Please contact the chairs if you have ideas for future webinars that you’d like considered within this series.
2018 Events

“Unlocking the ‘Omics Archive: Enabling Toxicogenomic/Proteomic Investigation from Archival Samples (ID 137) ” - SOT 2018 Roundtable Session
3/14 - San Antonio, TX 

“Applied Genetic Toxicity for Regulatory Decision Making: The Road Ahead” - A joint workshop with the HESI Genetic Toxicology Committee & EEMGS
3/22 & 3/23 - Potsdam, Germany

Li HH, Chen R, Hyduke DR, Williams A, Frötschl R, Ellinger-Ziegelbauer H, O’Lone R, Yauk CL, Aubrecht J, Fornace Jr. AJ. (2017). “Development and validation of a high-throughput transcriptomic biomarker to address 21st century genetic toxicology needs.” PNAS 2017 114: E10881-E10889. Find it here!

Wehmas LC, Wood CE, Gagne R, Williams A, Yauk C, Gosink MM, Dalmas D, Hao R, O’Lone R, Hester S. (2017). “Demodifying RNA for Transcriptomic Analyses of Archival Formalin-Fixed Paraffin-Embedded Samples.” Toxicological Sciences , kfx278. Find it here!  
HESI Staff
Syril Pettit
HESI Executive Director

Lauren Peel
Scientific Program Associate